Pneumococcal Vaccine and Antimicrobial Resistance in Children

Abstract & Commentary

By Hal Jenson, MD, Chief Academic Officer, Baystate Health Professor of Pediatrics and Dean of the Western Campus of Tufts University School of Medicine

Dr. Jenson is on the speaker's bureau for Merck.

Synopsis: Use of the 7-valent pneumococcal vaccine has resulted in substantial reductions in the prevalence of pneumococcal isolates contained in the vaccine. Antimicrobial resistance among nonvaccine strains in the respiratory tract is increasing.

Source: Farrell DJ, et al. Increased antimicrobial resistance among nonvaccine serotypes of Streptococcus pneumoniae in the pediatric population after the introduction of 7-valent pneumococcal vaccine in the United States. Pediatr Infect Dis J. 2007;26:123-128.

Streptococcus pneumoniae isolates were collected from children (<14 yrs of age) with community-acquired respiratory tract infections (acute otitis media, community-acquired pneumonia, acute maxillary sinusitis, or acute rhinosinusitis) from 2000-2004 in 112 centers in 38 states. Cultures included blood, sputum, bronchoalveolar lavage fluid, middle ear fluid, sinus aspirates, and nasopharyngeal swabs or aspirates. Serotyping was performed by the Neufeld Quellung reaction and antimicrobial susceptibilities were determined in a central laboratory according to Clinical Laboratory Standards Institute standards.

The proportion of isolates covered by the PCV7 vaccine decreased from 65.5% in 2000-01 to 27.0% in 2003-04 when the most common serotypes were nonvaccine serotypes 19A (19%), 6A (7.8%), 3 (7.6%), 15 (6.3%), and 35B (5.8%), and vaccine serotype 19F (12.7%). Nonvaccine serotype 19A expressing the erm(B) + mef(A) macrolide resistance genotype increased from 7.8% to 45.5%. Antimicrobial resistance among blood isolates remained constant but increased among respiratory tract isolates for penicillin (resistant: 12.7% to 16.1% [P = 0.0857]; intermediate susceptibility: 20.1% to 31.5% [P < 0.0001]), erythromycin (21.2% to 31.6% [P < 0.0001]), amoxicillin-clavulanate (1.4% to 5.8% [P < 0.0001]), and multidrug resistance to >2 antimicrobial classes (24.6% to 31.6% [P = 0.0034]). A nonsignificant increase was seen for trimethoprim-sulfamethoxazole (25.1% to 28.4% [P = 0.17]) and only 1 isolate, in 2003-04, was resistant to telithromycin.

Commentary

These studies do not measure disease burden but document that PCV7 has had a dramatic impact on pneumococcal serotype prevalence among children in the 4 years since its introduction. There have been reductions of vaccine serotypes and emergence of nonvaccine serotypes as the predominant pneumococcal serotypes. This has occurred in both young children < 2 yr of age and among older children 3-14 yr of age. There is some geographic variation among different states reflecting different rates of PCV7 immunization.

Initial surveillance data after the introduction of PCV7 suggested that pneumococcal penicillin and erythromycin resistance declined in isolates from children. Disappointingly, these data now document that resistance to penicillin, macrolides, amoxicillin-clavulanate, trimethoprim-sulfamethoxazole, and multidrug resistance all increased in pneumococcal respiratory tract isolates from 2000 to 2004. There was a 3-fold increase from 2000 to 2004 in the prevalence of erm(B) and mef(A) isolates, primarily nonvaccine serotype 19A and vaccine serotype 19F, most of which are resistant to most antimicrobial classes. (PCV7 has lower efficacy against serotype 19F compared to other vaccine serotypes.)

The changes in pneumococcal serotype distribution resulting from use of PCV7 and the changes in antimicrobial resistance from indiscriminate or inappropriate antimicrobial use are each contributing to a dynamic picture of pneumococcal epidemiology.